K. N. Lai

Effect of Hemodialysis on Protein C, Protein S, and Antithrombin III Levels

We studied the effect of hemodialysis on natural coagulation inhibitors including protein C (PC), protein S (PS), and antithrombin III (AT III), as well as the correlations between the antigen level (immunological activity) and functional activity of individual coagulation inhibitor. Plasma AT III, PS, and PC were measured in 20 uremic patients on maintenance hemodialysis immediately before, during, and after dialysis treatment. These values were compared with those obtained from 20 matched healthy controls. Plasma PC and total PS antigen levels were measured by enzyme immunoassay. The plasma AT III antigen level was determined by Laurell rocket immunoelectrophoresis. Functional activities of PC and AT III were determined by the amidolytic method. Free PS antigen level was quantitated by measuring the free PS-related antigen after the sample was treated with polyethylene glycol to remove the C4b-binding protein. Uremic patients on maintenance hemodialysis had a higher total PS antigen level, but a lower free PS antigen level compared with the controls. Both the antigen level and functional activity of AT III in uremic patients were significantly lower than those of controls. Their predialysis plasma PC antigen level and functional activity were not different from those of normal controls. A significant correlation between the antigen level and functional activity of PC, PS, and AT III was demonstrated in healthy controls, but not in hemodialysis patients. No significant change in the level of AT III or PS was observed with hemodialysis, but a progressive increase of functional activity of PC was documented with hemodialysis. Furthermore, the coefficient of correlation between the antigen level and functional activity of PC improved significantly with dialysis treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Independent effects of residual renal function and dialysis adequacy on nutritional status and patient outcome in continuous ambulatory peritoneal dialysis

Dialysis adequacy has a major impact on outcome of continuous ambulatory peritoneal dialysis (CAPD) patients. However, there is a substantial confounding effect by residual renal function in most studies. We differentiated the effects of dialysis adequacy from those of residual renal function on nutritional status and outcome of CAPD patients. We identified 168 CAPD patients treated in our center between September 1995 and December 1996 and categorized them into three groups: 49 patients with an average total Kt/V of 1.93 +/- 0.18 and a median residual glomerular filtration rate (GFR) of 0. 07 mL/min/1.73 m(2) in the dialysis-dependent (DD) group; 48 patients with an average total Kt/V of 2.03 +/- 0.25 and a residual GFR of 2. 33 mL/min/1.73 m(2) in the residual renal function (RRF) group; and 71 patients with an average total Kt/V of 1.38 +/- 0.22 and a residual GFR of 0.05 mL/min/1.73 m(2) in the control (CTL) group. They were followed-up for 1 year to compare baseline nutritional status and 1-year morbidity. Baseline normalized protein catabolic rates (NPCR) are 1.00 +/- 0.20 and 0.96 +/- 0.19 (for RRF and DD, respectively) versus 0.89 +/- 0.16 g/kg/d for CTL (P < 0.01). Percentage lean body mass (%LBM) was 71.6 +/- 9.8 and 71.5 +/- 10.0 (for RRF and DD, respectively) versus 65.2 +/- 8.5% for CTL (P < 0. 001). No difference was seen in the nutritional status between RRF and DD groups. Duration of hospitalization for 1 year was 6.9 +/- 11. 8 days in the RRF group versus 14.9 +/- 25.1 in the DD and 10.6 +/- 11.6 days in the CTL groups (P < 0.05). The peritonitis rate was 44. 4 patient-months for the RRF group, versus 13.6 for the DD and 12.9 for the CTL groups (P < 0.05). There also was a trend toward superior 1-year technique survival in the RRF group, but the number of observations was small. There was no difference in duration of hospitalization, peritonitis rate, and technique survival between the DD and CTL groups. Short-term morbidity in patients without residual renal function appears to be independent of total Kt/V, although Kt/V may have some effects on nutritional status. The assumption that renal and peritoneal clearances are equivalent must be carefully reexamined. Further studies on the effect of dialysis adequacy in patients without residual renal function are urgently needed.

Cytokine production by peripheral blood mononuclear cells in IgA nephropathy.

The regulation of cytokine production and T cell proliferation by other cytokines is mandatory in mediating inflammatory responses but the full understanding is far from complete. We have previously reported increased production of IL‐2 and IL‐2 receptors (IL‐2R) in IgA nephropathy. The present study was undertaken to examine other cytokine production during T cell activation in IgA nephropathy. Peripheral blood mononuclear cells (PBMC) from 17 IgA nephritic patients and 14 controls were cultured with phytohaemagglutinin and phorbol myristate acetate for 48 h for maximal cytokine production. IL‐2Rs and IL‐4 receptors (IL‐4Rs) expressed on cultured PBMC were studied by a radioimmunoassay using monoclonal antibodies against these receptors. Although the total cellular IL‐2R expression and percentages of T helper and T suppressor cells did not differ between the patients and controls, there was a significant increase in activated T helper cells expressing IL‐2R in patients with IgA nephropathy. The total cellular IL‐4R expression was elevated in IgA nephritic patients (P<0.005). IL‐2 production by PBMC was raised in IgA nephritic patients compared with controls (P<0.05) but no difference in IL‐4 or IL‐6 production was observed. The interferon‐gamma production by PBMC was significantly increased in patients with IgA nephropathy (P< 0.025). No correlation was observed between individual cytokine levels. Our data suggest there are selective increases in cytokine production in IgA nephropathy.

DIALYSIS ADEQUACY OF ASIAN PATIENTS RECEIVING SMALL VOLUME CONTINUOUS AMBULATORY PERITONEAL DIALYSIS

The usage of three × 2 liter daily exchanges is adopted as the standard CAPD regime in Hong Kong over the last 10 years due to budgetary constraint. This dialysis prescription is considered suboptimal in Western standard. However, the necessity of maintaining Kt/V > 1.7 for CAPD dialysis adequacy is not unanimously agreed. We performed a cross-sectional study of 117 patients on CAPD. Seventy-eight percent of our patients had 3 × 2 liter daily exchange while the rest had 4 daily exchanges. Fifteen percent of patients were diabetic. Patients with Kt/V < 1.7 were similar to those with Kt/V > 1.7 in age, duration of CAPD, BUN, plasma creatinine, albumin, peritonitis rate, and incidence of hypertension. Patients with Kt/V ≥ 1.7 had higher hemoglobin, higher nPCR, more residual renal function; and more of them received 4 daily exchanges. Their peritoneal permeability did not differ. Their employment and rehabilitation status was also similar. Our 5-year survival was 79% despite a lower Kt/V. Notably, the protein catabolic rate of our patients was higher than that in Western patients. This is likely due to dietary difference. Our study suggests small-volume dialysis may be acceptable in Asian population with smaller body size given the financial constraint.

Increase of both circulating Th1 and Th2 T lymphocyte subsets in IgA nephropathy

IgA nephropathy (IgAN), characterized by glomerular deposition of IgA and frequently elevated plasma IgA levels, has increased T helper cell activity. In vitro measurement of cytokines in supernatant of cultured peripheral lymphocytes revealed conflicting findings. We examined the profile of cytokine mRNA expressed in purified CD4+ cells in patients with IgAN in order to study their pattern of Th1 (releases IL‐2 and interferon‐gamma (IFN‐γ)) and Th2 (releases IL‐4 and IL‐5) T cell response. We assessed the circulating CD4+ T cells in patients and normal controls by the expression of messenger RNA (mRNA) for IL‐2, IL‐4, IL‐5 and IFN‐γ. The cytokine mRNAs were analysed with reverse transcription‐polymerase chain reaction and were measured semiquantitatively by using a housekeeping gene, β‐actin. Compared with the control subjects, CD4+ T lymphocytes from patients with IgAN expressed a higher level of IL‐2 mRNA (p=0.007), IFN‐γ mRNA (P = 0.04), IL‐4 mRNA (p = 0.048), and IL‐5 mRNA (P=0.016). Within these patients with IgAN, a good correlation was demonstrated between the gene expression of cytokines in Th1 or Th2 cells. The IL‐2 mRNA levels in Th1 cells from these patients with IgAN also correlated significantly with the IL‐4 or IL‐5 mRNA levels in their Th2 cells. Our study revealed IgAN is associated with activation in circulating lymphocytes of the IL‐2, IFN‐γ, IL‐4 and IL‐5 gene cluster, a pattern compatible with activation of both the Th1‐ and Th2‐like T lymphocyte population. The increased transcription of these cytokine genes may be contributory to the immunopathologic findings in IgAN.

Glomerulonephritis Associated With Takayasu's Arteritis: Report of Three Cases and Review of Literature

Clinical features and pathologic findings of the kidney in three patients with Takayasus arteritis and associated nephritis are described. Clinical evidence of renal disease included proteinuria, hematuria, and a reduction of glomerular filtration rate. Renal histology revealed mesangial proliferative glomerulonephritis in one patient and minor glomerular abnormalities in the other two. The clinical course of the glomerulopathy is slow, yet progressive, and the corticosteroid and immunosuppressive therapy appear to delay the progression of the glomerular damage. In one patient in whom repeated examination of the kidney after corticosteroid and immunosuppressive treatment was possible, the glomerular pathology remained unchanged. This report of three patients with Takayasus arteritis and concomitant nephritis supports the previous speculation of the association between these two conditions. The glomerular, vasculitic, and arteriopathic involvements in these patients may suggest a common immunologic mechanism.

Xanthomonas maltophilia peritonitis in uremic patients receiving continuous ambulatory peritoneal dialysis

Xanthomonas maltophilia peritonitis has been only occasionally reported in patients receiving continuous ambulatory peritoneal dialysis. We present a series of six cases of peritonitis caused by such bacteria, accounting for 1.5% of all peritonitis episodes encountered in our renal unit over the past 5 years. Recent bacterial peritonitis treated with broad-spectrum antibiotics was the major risk factor, and the outcome was poor with medical treatment alone. Secondary peritonitis, especially fungal, was common and probably related to the prolonged course of antibiotics. All patients eventually required removal of the catheter, either because the effluent failed to clear up or because of secondary peritonitis. We suggest that X maltophilia peritonitis be treated with double antibiotics as soon as it is diagnosed. To prevent the development of superimposed infection after prolonged administration of antibiotics, the Tenckhoff catheter should be removed if the peritonitis fails to respond to a short course of antibiotics.

Measured-to-predicted creatinine generation ratio increases with time and decline in residual renal function in continuous ambulatory peritoneal dialysis

The expression of measured-to-predicted creatinine generation ratio (M/P) has been proposed as an index of compliance in continuous ambulatory peritoneal dialysis (CAPD) patients. Although M/P may not be sensitive enough for cross-sectional study, serial monitoring has been suggested to identify noncompliance. We attempted to evaluate serial changes of M/P from a nonselected group of CAPD patients. Sixty-three patients, all followed up for 2 years, were reviewed retrospectively. Their M/P ratios at years 0 and 2 were computed and compared. Baseline M/P had a normal distribution with a mean of 0.96 +/- 0.26. There was significant correlation between baseline M/P and residual glomerular filtration rate (GFR; r = -0.81; P < 0.0001). There were weak correlations between M/P and duration of dialysis (r = 0.52; P < 0.0001), body weight (r = -0.52; P < 0.0001), Kt/V (r = 0.31; P < 0.02), weekly creatinine clearance normalized to body surface area (r = 0.53; P < 0.0001), and serum albumin level (r = -0. 28; P < 0.05). After 2 years, M/P increased in 56 of 63 patients (88. 9%). Average M/P increased from 0.96 +/- 0.26 to 1.31 +/- 0.27 (P < 0.0001). Multivariant analysis showed M/P at year 0, which was largely determined by residual GFR, was the only independent factor affecting increase in M/P from year 0 to year 2. The general trend of increasing M/P was still present when only anuric patients were analyzed, although that was not statistically significant (1.21 +/- 0.14 to 1.32 +/- 0.24; P = 0.12). The finding of increasing M/P with time in CAPD patients, particularly those with significant residual renal function, suggests M/P may not be a reliable indicator of noncompliance, even for serial follow-up of the same patient. Better methods for assessment of compliance in CAPD patients are required.

Renal Failure and Heatstroke

We report a fatal case of heatstroke in an obese boy who developed multi-organ failure. Six other cases of exertional heatstroke admitted to our hospital over the last 5 years were also reviewed. All of them showed some degree of renal impairment. The causes of renal failure are multifactorial, with rhabdomyolysis being the major mechanism. All cases except one responded to alkaline diuresis without the need for dialysis. Continuous venovenous hemofiltration appeared to be a good alternative in hemodynamically unstable patients. Renal function recovered completely after varying intervals in all surviving cases. Interestingly, rhabdomyolysis in our heatstroke patients was usually associated with hypokalemia or normokalemia instead of hyperkalemia. Mortality in our series was largely related to the long duration of hyperthermia and coma, the severity of disseminated intravascular coagulation, and the presence of cardiogenic shock and severe acidosis.

Recurrent acute pancreatitis induced by isoniazid

A 31-year-old man on haemodialysis who developed recurrent attacks of acute pancreatitis during the treatment of pulmonary tuberculosis is presented. The pancreatitis rapidly subsided once isoniazid was withdrawn, but the problem recurred again upon reintroduction of the drug. There was no further recurrence during successful treatment with full doses of rifampicin and pyrazinamide for 1 year.